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Exposure to hyperoxia induces p53 expression in mouse lung epithelium
M A O'Reilly1, R J Staversky, B R Stripp
1Department of Pediatrics (Neonatology), School of Medicine and Dentistry, University of Rochester, New York 14642, USA. oreillym@envmed.rochester.edu
American Journal of Respiratory Cell and Molecular Biology
|February 3, 1998
Summary
Exposure to hyperoxia causes DNA damage in lung epithelial cells, leading to increased p53 protein accumulation. This response indicates cellular injury and functional changes in the pulmonary epithelium.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Free radical exposure causes DNA strand breaks and p53 protein accumulation.
- Oxidants are known to injure pulmonary epithelial cells.
- p53 protein accumulation can lead to cell cycle arrest and apoptosis.
Purpose of the Study:
- To investigate if hyperoxia (high oxygen exposure) induces DNA strand breaks in lung epithelium.
- To determine if hyperoxia increases p53 expression in lung cells.
- To assess the functional consequences of hyperoxia on pulmonary epithelial cells.
Main Methods:
- Adult male C57Bl/6J mice were exposed to hyperoxia (>95% oxygen) for 72 hours.
- DNA integrity was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
- p53 protein and specific gene expression (SP-B, Clara cell secretory protein, cytochrome P-450 2F2) were analyzed using Western and Northern blot techniques.
Main Results:
- Hyperoxia exposure significantly increased DNA strand breaks in distal bronchiolar and alveolar epithelial and endothelial cells.
- p53 protein levels markedly increased in the nuclei and cytoplasm of distal bronchiolar and alveolar epithelial cells.
- Hyperoxia elevated total lung p53 protein but not its mRNA levels, suggesting post-transcriptional regulation.
Conclusions:
- Hyperoxia induces DNA damage in pulmonary epithelial cells.
- The accumulation of p53 protein in response to hyperoxia indicates cellular injury.
- Hyperoxia causes changes in pulmonary epithelial cell-specific gene expression, supporting the concept of cellular damage and functional impairment.